Results

22 studies that reported on the association between prenatal environmental risk factors
and infants born with ARM were included in this review. These were conducted in the
United States of America (n = 12), Spain (n = 2), Sweden (n = 2), the Netherlands
(n = 2), Japan (n = 1), France (n = 1), Germany (n = 1) and Hungary (n = 1). However,
only few of these studies reported on the same risk factors. Studies were heterogeneous
with respect to case numbers, control types and adjustment for covariates. Consistently
increased risks were observed for paternal smoking and maternal overweight, obesity
and diabetes, but not for maternal smoking and alcohol consumption. In meta-analyses,
pooled odds ratios (95% confidence intervals) for paternal smoking, maternal overweight,
obesity, pre-gestational and gestational diabetes were 1.53 (1.04-2.26), 1.25 (1.07-1.47),
1.64 (1.35-2.00), 4.51 (2.55-7.97) and 1.81 (1.23-2.65), respectively.

Conclusion

Evidence on risk factors for ARM from epidemiological studies is still very limited.
Nevertheless, the few available studies indicate paternal smoking and maternal overweight,
obesity and diabetes to be associated with increased risks. Further, ideally large-scale
multicentre and register-based studies are needed to clarify the role of key risk
factors for the development of ARM.